A conserved RNA regulates miRNA turnover and animal behavior through a near-perfect miRNA site
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE98707
PROVIDER: PRJNA385967 | ENA |
REPOSITORIES: ENA
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Project description:Metazoan high complementarity microRNA (miRNA) binding sites can induce miRNA turnover through 3′ tailing and trimming, however the in vivo importance of this mechanism remains unknown. Here, we show that a transcript harboring a highly complementary and deeply conserved miRNA binding site for miR-29 controls zebrafish and mouse behavior. This brain-enriched transcript originated in distal vertebrates as a long noncoding RNA, which we called libra (lncRNA involved in behavioral alterations), and evolved to the protein-coding gene known as NREP in mammals where the miR-29 binding site is located within the 3′UTR. libra-deficiency results in viable fish that manifest abnormal exploration behavior. To determine if the Nrep transcript retained the regulatory noncoding function and to define the contribution of the highly complementary miR-29 binding site, we generated the NrepmiR-29scr allele in mice where the sequence of the site was scrambled to specifically uncouple Nrep function from miR-29 regulation. We show that the Nrep miR-29 binding site restricts miR-29b expression in the cerebellum. The ectopic miR-29b expression in NrepmiR-29scr mice is associated with altered cerebellum function and behavior. We finally show that the near-perfect miRNA site triggers miR-29b turnover through 3′ trimming. In summary, we demonstrate the first example of an endogenous RNA-directed miRNA degradation event in vivo that is required for normal animal behavior.
2018-01-14 | GSE98707 | GEO
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Project description:We measured miRNA turnover rates in 8 mammalian cell types post transcription inhibitors ActinomycinD (ActD) or 5,6-Dichlorobenzimidazole 1-β-D-ribofuranoside (DRB) treatment with miRNA expression profiling, generating 218 expression profiles on 528 endogenous miRNAs.
2015-02-05 | GSE46877 | GEO
Project description:HDMYZ cells were treated with 4ug/ml ActD for 0, 1, 4 and 12 hours. Small RNAs of 15-40 bases were gel-purified from 5 ug total RNA, and subjected to multiplex Illumina small RNA library preparation. Small RNA libraries were sequenced on a HiSeq2000 (Illumina). Measure miRNA expression level at 0, 1, 4, 12 hours post ActinomycinD treatment to examine miRNA turnover pattern.
2015-02-05 | E-GEOD-60036 | biostudies-arrayexpress
Project description:We measured miRNA turnover rates in 8 mammalian cell types post transcription inhibitors ActinomycinD (ActD) or 5,6-Dichlorobenzimidazole 1-M-NM-2-D-ribofuranoside (DRB) treatment with miRNA expression profiling, generating 218 expression profiles on 528 endogenous miRNAs. Cells were plated in six-well plates at around 200,000 cells/well. A media change was performed one day after plating. ActD and DRB treatment were started after confluency (around two days after plating) for 0, 2, 4, 6, 12, and 24 hours post treatment with biological duplicate (ActD treatment) or biological triplicate (DRB treatment). The concentration of ActD and DRB for different cell lines were titrated to achieve rapid c-myc down-regulation after 2 hours of ActD and DRB treatment. After treatment at indicated time points, cells were washed with PBS once and lysed in TriZol reagent immediately (Invitrogen). RNA extraction was performed following the manufacturerM-bM-^@M-^Ys protocol. miRNA profiling was performed using a Luminex bead-based method.
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Project description:Genome-wide miRNA turnover profile in various cell types after transcription inhibition
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Project description:The decapping scavenger enzyme DcpS is known for its role in hydrolyzing the cap structure following mRNA degradation. Recently, we discovered a new function in miRNA degradation activation for the ortholog of DcpS in C. elegans. Here we show that human DcpS conserves its role in miRNA turnover. In human cells, DcpS is a nucleocytoplasmic shuttling protein and that DcpS activates miRNA degradation independently of its scavenger decapping activity in the cytoplasmic compartment. We also demonstrate that this new function for DcpS requires the contribution of the 5’-3’ exonuclease Xrn2. Our findings support a conserved role of DcpS as a modulator of miRNA turnover in animals.
2016-05-23 | GSE69591 | GEO
Project description:Gld2, a noncanonical cytoplasmic poly(A) polymerase, interacts with the RNA binding protein CPEB1 to mediate polyadenylation-induced translation in dendrites of cultured hippocampal neurons. Depletion of Gld2 from the hippocampus leads to a deficit in long-term potentiation evoked by theta burst stimulation. At least in mouse liver and human primary fibroblasts, Gld2 also 3' monoadenylates and thereby stabilizes specific miRNAs, which enhance mRNA translational silencing and eventual destruction. These results suggest that Gld2 would be likely to monoadenylate and stabilize miRNAs in the hippocampus, which would produce measurable changes in animal behavior. We now report that using Gld2 knockout mice, there are detectable alterations in specific miRNA monoadenylation in the hippocampus when compared to wild type, but that these modifications produce no detectable effect on miRNA stability. Moreover, we surprisingly find no overt change in animal behavior when comparing Gld2 knockout to wild-type mice. These data indicate that miRNA monoadenylation-mediated stability is cell type-specific and that monoadenylation has no measurable effect on higher cognitive function.
2018-05-09 | GSE114259 | GEO
Project description:Turnover and exchange of nucleosomal histones and their variants, a process long believed to be static in post-replicative cells, remains largely unexplored in brain. Here, we describe a novel mechanistic role for HIRA (histone cell cycle regulator) and proteasomal degradation associated histone dynamics in the regulation of activity-dependent transcription, synaptic connectivity and behavior. We uncover a dramatic developmental profile of nucleosome occupancy across the lifespan of both rodents and humans, with the histone variant H3.3 accumulating to near saturating levels throughout the neuronal genome by mid-adolescence. Despite such accumulation, H3.3 containing nucleosomes remain highly dynamic–in a modification independent manner–to control neuronal- and glial- specific gene expression patterns throughout life. Manipulating H3.3 dynamics in both embryonic and adult neurons confirmed its essential role in neuronal plasticity and cognition. Our findings establish histone turnover as a critical, and previously undocumented, regulator of cell-type specific transcription and plasticity in mammalian brain. All RNA-seq samples were generated to test the impact of neuronal activity/adult physiological plasticity on histone turnover turnover mediated alterations in mRNA expression in the central nervous system. This was tested in cultured neurons and astrocytes, and embryonic/adult brain tissues
2015-06-23 | E-GEOD-69807 | biostudies-arrayexpress
Project description:IGF2BP1, a conserved regulator of RNA turnover in cancer
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